Hemangiomas and angiosarcomas of the breast: diagnostic utility of cell cycle markers with emphasis on Ki-67

Arch Pathol Lab Med. 2007 Apr;131(4):538-44. doi: 10.5858/2007-131-538-HAAOTB.

Abstract

Context: Vascular tumors comprise a minor subgroup of tumors arising in the breast and represent variants of hemangiomas and angiosarcomas. Diagnostic challenges may arise when differentiating hemangiomas from types I and II angiosarcomas. Ki-67 expression has been used as an adjunct to distinguish between benign and malignant lesions exhibiting histologic overlap at various anatomic sites.

Objective: To investigate the utility of Ki-67 and other cell cycle regulatory proteins (S-phase kinase-associated protein 2 [Skp2], p27, and cyclin D1) in the differential diagnosis of mammary vascular lesions.

Design: Thirty-four vascular tumors (21 hemangiomas and 13 angiosarcomas) of the breast were studied. The Ki-67 index and immunoreactivity for Skp2, p27, and cyclin D1 were determined in each case. Appropriate statistical methods were used.

Results: The mean value of Ki-67 index was statistically different when comparing hemangiomas and angiosarcomas (P < .001). Angiosarcomas were typically positive for Skp2, whereas hemangiomas were negative (P < .001). Sensitivity and specificity cutoffs for Ki-67 index to distinguish hemangiomas from angiosarcomas showed a candidate cutoff point of 175. The mean values of Ki-67 of low-grade angiosarcomas were significantly different from all hemangiomas (P < .001) and also different from the subset of atypical hemangiomas (P = .02). Sensitivity and specificity cutoffs for Ki-67 index to distinguish all hemangiomas from low-grade angiosarcomas showed a candidate cutoff point between 150 and 175. Among angiosarcomas, positivity for Ki-67 was inversely related to that of p27 but not to Skp2 or cyclin D1. This was also true among hemangiomas.

Conclusions: Ki-67 index can be used as a diagnostic tool to distinguish between benign and malignant vascular lesions of the breast. This can be particularly helpful in cases of histologic overlap such as low-grade angiosarcoma and hemangioma.

MeSH terms

  • Biomarkers, Tumor / analysis
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms, Male / diagnosis*
  • Breast Neoplasms, Male / metabolism
  • Cell Cycle
  • Cyclin D1 / metabolism
  • Diagnosis, Differential
  • Female
  • Hemangioma / diagnosis*
  • Hemangioma / metabolism
  • Hemangiosarcoma / diagnosis*
  • Hemangiosarcoma / metabolism
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism*
  • Male
  • Middle Aged
  • Proliferating Cell Nuclear Antigen / metabolism
  • S-Phase Kinase-Associated Proteins / metabolism
  • Sensitivity and Specificity

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Proliferating Cell Nuclear Antigen
  • S-Phase Kinase-Associated Proteins
  • p27 antigen
  • Cyclin D1